Angiotensin II stimulates synthesis of endothelial nitric oxide synthase.
Previous studies have suggested that NO may play an important role in protecting the renal vessels from angiotensin II (ANGII)-mediated vasoconstriction. One possible mechanism for this interaction is that ANGII could stimulate NO production in the kidney by increasing endothelial NO synthase (NOS III). The present studies were performed in rats to determine whether acute or chronic elevations in ANGII are associated with enhanced renal NOS III mRNA or protein synthesis. In both acute and chronic studies captopril (20 microg/kg/min) was given I.V. to inhibit endogenous ANGII production. Acute suprarenal infusion of ANGII (8 ng/kg/min) for 110 minutes had no effect on arterial pressure but decreased GFR and renal plasma flow by 20% and 30%, respectively, and increased renal vascular resistance by 70%. Acute ANGII increased renal NOS III mRNA by 70% (as determined by ribonuclease protection assay), but had no effect on renal NOS III protein concentration (as detected by Western blot analyses). In contrast, chronic infusion of ANGII (5 ng/kg/min) for 10 days, increased arterial pressure by 30% and tended to reduce GFR and renal plasma flow. Chronic ANGII had no effect on renal NOS III mRNA levels, but increased NOS III protein by 90%. These data suggest that ANGII can stimulate NOS III synthesis and suggest that this may be one of the mechanisms whereby AngII may enhance NO production.
Hennington
B S
BS
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Zhang
H
H
Miller
M T
MT
Granger
J P
JP
Reckelhoff
J F
JF
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply / Q000502:physiology; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D012333:RNA, Messenger; D000804:Angiotensin II; D002216:Captopril; D019001:Nitric Oxide Synthase